Sunday, November 10, 2019

Bruice Organic Chemistry Note #6: Isomers, The Arrangement of Atom in Space

What are isomers? Isomers are compounds with the same molecular formula but have different structures.  There are so many types of isomers that I have mentioned briefly in this post. Through this post, I will explain more detail. 

There are two classes of isomers: constitutional isomers and stereoisomers. Constitutional isomers are compounds that differ from the way how their atoms are connected, for example, alcohol and ether. Meanwhile, stereoisomers are compounds that their atoms are connected in the same way, but how arranged in space is different. Wait, stereoisomers itself has two classes: Conformational isomers and configurational isomers. 

Conformational isomers (conformers) are stereoisomers that rapidly interconvert at room temperature, but these conformers can not be separated. While configurational isomers are stereoisomers that can not be interconverted unless the covalent bonds are broken so these isomers can be separated. 

In conformational isomers, there are two types, conformational isomers due to rotation about carbon-carbon single bonds (staggered, eclipsed, chair, and boat) and those due to amine inversion. 

For configurational isomers case, there are two types, configurational isomers-cis-trans isomers and isomers that contain asymmetric centers. 

Now, let's talk about configurational isomers, start from cis-trans isomers. Cis-trans isomers is also called as geometric isomers. This isomers result from restricted rotation. You may only familiar with the rotation caused by double bond, but actually, it may also be caused by cyclic structure. These isomers can be separated as they have different physical properties such as different boiling points.

Now, you know how to name cis-trans isomers, simply by comparing the substituent whether the hydrogens are on the same side (cis) or not (trans). Then, how if the substituents don't have hydrogen, how to name it? 

You can use E,Z system, E for entgegen (opposite), Z for zusammen (together), these are from German language. To know which one is E and which one is Z, we have to look at the atomic numbers of the atom bonded directly to the sp2 carbon. The higher number of atomic number becomes a high priority. If the high priority of two atoms is on the same side, then it is Z, and vice verca.

How if, the atomic numbers of two atoms are the same, so we can not differentiate, as there is a tie, then compare the atomic numbers of the atom bonded next to it. 

How if the atom bonded is doubly bonded or triply bonded, then consider the atom to have single bond to two or three of those atoms.

Another case, how if the atom has the same atomic numbers but different mass numbers, then treat the higher mass number as a higher priority.

Now, let's move to the discussion of configurational isomers caused by asymmetric center. Also called as chiral center, asymmetric center is a carbon that is bonded with different 4 substituents. Because of this structure, a compound with asymmetric center can exist as two enantiomers. Enantiomers mean molecules that are mirror image each other but not superimposable. These two molecules are the same in physical properties (boiling points, melting points, solubilities, and so on) different in some properties (for example, biological properties). For these chiral molecules, different with conformational isomers, they can be separated by certain methods.

Asymmetric center is also called as stereocenter or stereogenic center. Stereocenter means the atom is the location where the interchange of two groups produced. But, it should be pointed out that, all asymmetric center are stereocenters, but not all stereocenters are asymmetric center as cis-trans isomers are also having stereocenters. 

How to name two enantiomers? We can use R,S system. R for rectus (right), and S for sinister (left), this is from Latin. So, the naming is based on comparing the atomic number. Firstly, by drawing the molecule with perspective formula which solid and hatched wedge can be used. Then put the highest priority (the highest in atomic number as number 1, and the lower comes as number 2, and so others). Assign the lowest priority as the substituent bonded with hatched wedge. The solid line must always next to the hatched wedge and the hatched wedge must always be drawn on top of the solid line. 

The last, draw an arrow in the direction from the highest priority to the lowest priority, from 1 to 2 to 3. If the direction is clockwise, then R configuration, if counterclockwise, S configuration.

To compare the priority, the assignment is the same as cis-trans isomers, so if two substituents have the same atomic number then compare with the atom bonded next to it. 

I mentioned before that two enantiomers have some different properties. One of them is different in optical rotation. I believe you may already know this. If it can rotate to the right, it is indicated by (+), if left, then (-). It doesn't mean if a molecule with R configuration is (+) or S is (-) as to know the optical rotation requires experimental measurement. So, the naming of the structure will be like the picture below.

An enantiomer will have observed specific rotation. If the number is not shown the same, for example, less than what it should be, means that the sample is not enantiomerically pure, the sample is in a racemic mixture. To measure the purity of the sample, %ee (enantiomeric excess) will answer it. 

To calculate % ee, below is the equation. If a sample, the observed specific rotation is +23.1, but the actual observed is +9.2, then the enantiomeric excess is shown below.

This example showed that the racemic mixture has 40% enantiomeric excess, for example, 40% is the excess of S enantiomer and 60% is the racemic mixture. So from the racemic mixture, half is in S configuration, the other half is R configuration. In total, 40% + 30% is S enantiomer (70%).

Next, let's discuss how if a molecule has more than one asymmetric center. How to name it? How about the property?

This is called as diastereomers. Look at the difference below. 

Stereoisomers 1 and 3, 1 and 4, 2 and 3, 2 and 4 are pairs of diastereomers. Meanwhile, 1 and 2 and 3 and 4 are still enantiomers as it is mirror-image each other. If even though the molecules have two asymmetric centers and mirror-image each other and hydrogen is on the same side, they are called erythro enantiomers, but if mirror-image each other and hydrogen is not on the same side, called as threo enantiomers.

Do you believe that every compound that has asymmetric center are all optically active? The answer is no. Because there is a situation when a compound does have the asymmetric center but not optically active. The compound is called a meso compound. What does make it not optically active? Look at the picture below.

The compound has two asymmetric centers but both have the same substituents in all other parts, so make the mirror image superimposable. To make it easier to recognize meso compound, just put a plane of symmetry between those two asymmetric centers, if those are mirror-image each other means it is meso compound. So, there is no enantiomer. 

Anyway, how to name a compound with more than 1 asymmetric center? Just determine S,R system for each asymmetric center, then put it like the picture below.

As we have talked about meso compound, I would like you to notice that a compound with more than 1 asymmetric centers then will have like three stereoisomers: 1 meso compound and 2 enantiomers. Those 3 stereoisomers are different in some ways. See below comparison. 

In a certain part, I mentioned that different enantiomer will have different biological activity. Here is an example: (R)-(-)-carvone smells like spearmint, while (S)-(+)-carvone smells like caraway seed. This is because only specific enantiomer that can activate certain receptor in our body, so nose perceives differently for each enantiomer. 

I told you before too, that conformational isomers can not be separated but enantiomers can be separated. So, how? Through chromatography with special column packed with a chiral material that adsorbs organic compounds. Two enantiomers move through the column at different rates as they have different affinities for the chiral materials as right hand prefers right-hand glove so the one enantiomer will come out before the other one.

That's all from me, thank you for visiting. I am sorry if there is a mistake. All the explanation refer to this:

Bruice, P. Y. 2017. Organic Chemistry Eighth Edition. England: Pearson Education Limited.


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